Oncological safety of transanal total mesorectal excision (TaTME) for rectal cancer: mid-term results of a prospective multicentre study

Background There is no consensus regarding the gold standard technique for rectal cancer as Total Mesorectal Excision (TME) may be safely performed either by open or minimally invasive surgery. The laparoscopic approach, however, may carry technical difficulties. For this reason, a novel technique has emerged in the last decade combining a dual laparoscopic dissection (abdominal and transanal) to perform the TME technique (TaTME). When focusing on oncological outcomes, there is a lack of literature regarding mid-long term results. The aim of this study is to evaluate the mid-term oncological impact of TaTME for treating rectal cancer. Methods A prospective multicentre study was performed in four tertiary centres including consecutive patients who underwent TaTME for mid-low rectal cancer by the same group of experienced surgeons. The analysed data included pathological results on the quality of TME and mid-term oncological outcomes. Results In total, 173 patients were included throughout a study period of 6 years. Our series included 70% males and 68% of patients with neoadjuvant treatments. The median follow-up was 23 [15–37.5] months. Regarding pathological results, a complete TME was achieved in 72.8%, while circumferential and distal margins were affected in 1.4 and 1.1%, respectively. Five patients developed local recurrences (3%) and 8.1% presented distant disease during the follow-up. The 2-year disease-free survival and the overall survival rates were 88% and 95%, respectively. Conclusions There is currently a lack of evidence in the literature regarding TaTME and oncological outcomes with no data available from randomized clinical trials. In the meantime, the reported results from different multicentre series are controversial. This study showed positive mid-term outcomes at 2 years of follow-up and supported notable oncological outcomes with TaTME. However, it must be emphasized that previous experience in minimally invasive and transanal surgeries is essential for surgeons before intending to perform TaTME

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

How to perform an anastomosis following a low anterior resection by transanal total mesorectal excision surgery: from top to bottom techniques

Aim: The aim was to describe the range of possibilities and our group's clinical outcomes when performing different types of anastomosis during transanal total mesorectal excision (taTME). Method: A retrospective analysis was performed based on four taTME series from 2016 to 2021. Inclusion criteria were patients with rectal cancer in whom a sphincter-saving low anterior resection by taTME was performed. Four different techniques were employed for the anastomosis construction: (A) abdominal view, (B) transanal view, (C) hand-sewn coloanal anastomosis and (D) pull-through. Intra-operative and postoperative data were collected and compared. Results: A total of 161 patients were included. Tumour height was lower in groups C and D (4 [3-5] vs. 7 [6-8] group A vs. 6 [5-7] group B, P = 0.000), requiring a hand-sewn anastomosis. A transanal extraction of the specimen was more commonly performed in groups C and D (over 60% vs. 30% in groups A and B, P = 0.000). The rate of temporary stoma was similar between groups A, B and C (ranging from 84% to 98%) but was significantly lower in group D (P = 0.000). The overall rate of complications was similar between groups; however, group D had longer length of stay (15 days vs. 5-6 in groups A, B and C, P = 0.026). Conclusion: Every type of anastomosis construction after a taTME procedure seems to be safe and feasible and should be chosen based on surgeon's experience, tumour height and the length of the rectal cuff after the rectal transection. Colorectal surgeons should be familiar with these techniques in order to choose the one that benefits each patient the most

The impact of SARS-CoV-2 infection on the surgical management of colorectal cancer: lessons learned from a multicenter study in Spain

Objective: the aim of the study was to analyze the management of colorectal cancer (CRC) patients diagnosed with CRC or undergoing elective surgery during the period of the SARS-CoV-2 pandemic. Material and methods: a multicenter ambispective analysis was performed in nine centers in Spain during a four-month period. Data were collected from every patient, including changes in treatments, referrals or delays in surgeries, changes in surgical approaches, postoperative outcomes and perioperative SARS-CoV-2 status. The hospital's response to the outbreak and available resources were categorized, and outcomes were divided into periods based on the timeline of the pandemic. Results: a total of 301 patients were included by the study centers and 259 (86 %) underwent surgery. Five hospitals went into phase III during the peak of incidence period, one remained in phase II and three in phase I. More than 60 % of patients suffered some form of change: 48 % referrals, 39 % delays, 4 % of rectal cancer patients had a prolonged interval to surgery and 5 % underwent neoadjuvant treatment. At the time of study closure, 3 % did not undergo surgery. More than 85 % of the patients were tested preoperatively for SARS-CoV-2. A total of nine patients (3 %) developed postoperative pneumonia; three of them had confirmed SARS-CoV-2. The observed surgical complications and mortality rates were similar as expected in a usual situation. Conclusions: the present multicenter study shows different patterns of response to the SARS-CoV-2 pandemic and collateral effects in managing CRC patients. Knowing these patterns could be useful for planning future changes in surgical departments in preparation for new outbreaks

Multidisciplinary management of elderly patients with rectal cancer : recommendations from the SICG (Italian Society of Geriatric Surgery), SIFIPAC (Italian Society of Surgical Pathophysiology), SICE (Italian Society of Endoscopic Surgery and new technologies), and the WSES (World Society of Emergency Surgery) International Consensus Project

Background and aims Although rectal cancer is predominantly a disease of older patients, current guidelines do not incorporate optimal treatment recommendations for the elderly and address only partially the associated specific challenges encountered in this population. This results in a wide variation and disparity in delivering a standard of care to this subset of patients. As the burden of rectal cancer in the elderly population continues to increase, it is crucial to assess whether current recommendations on treatment strategies for the general population can be adopted for the older adults, with the same beneficial oncological and functional outcomes. This multidisciplinary experts' consensus aims to refine current rectal cancer-specific guidelines for the elderly population in order to help to maximize rectal cancer therapeutic strategies while minimizing adverse impacts on functional outcomes and quality of life for these patients. Methods The discussion among the steering group of clinical experts and methodologists from the societies' expert panel involved clinicians practicing in general surgery, colorectal surgery, surgical oncology, geriatric oncology, geriatrics, gastroenterologists, radiologists, oncologists, radiation oncologists, and endoscopists. Research topics and questions were formulated, revised, and unanimously approved by all experts in two subsequent modified Delphi rounds in December 2020-January 2021. The steering committee was divided into nine teams following the main research field of members. Each conducted their literature search and drafted statements and recommendations on their research question. Literature search has been updated up to 2020 and statements and recommendations have been developed according to the GRADE methodology. A modified Delphi methodology was implemented to reach agreement among the experts on all statements and recommendations. Conclusions The 2021 SICG-SIFIPAC-SICE-WSES consensus for the multidisciplinary management of elderly patients with rectal cancer aims to provide updated evidence-based statements and recommendations on each of the following topics: epidemiology, pre-intervention strategies, diagnosis and staging, neoadjuvant chemoradiation, surgery, watch and wait strategy, adjuvant chemotherapy, synchronous liver metastases, and emergency presentation of rectal cancer.Peer reviewe

Effect of topological cues on material-driven fibronectin fibrillogenesis and cell differentiation

Fibronectin (FN) assembles into fibrillar networks by cells through an integrin-dependent mechanism. We have recently shown that simple FN adsorption onto poly(ethyl acrylate) surfaces (PEA), but not control polymer (poly(methyl acrylate), PMA), also triggered FN organization into a physiological fibrillar network. FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules. In the present study, we investigate the influence of topological cues on the material-driven FN assembly and the myogenic differentiation process. Aligned and random electrospun fibers were prepared. While FN fibrils assembled on the PEA fibers as they do on the smooth surface, the characteristic distribution of globular FN molecules observed on flat PMA transformed into non-connected FN fibrils on electrospun PMA, which significantly enhanced cell differentiation. The direct relationship between the fibrillar organization of FN at the material interface and the myogenic process was further assessed by preparing FN gradients on smooth PEA and PMA films. Isolated FN molecules observed at one edge of the substrate gradually interconnected with each other, eventually forming a fully developed network of FN fibrils on PEA. In contrast, FN adopted a globular-like conformation along the entire length of the PMA surface, and the FN gradient consisted only of increased density of adsorbed FN. Correspondingly, the percentage of differentiated cells increased monotonically along the FN gradient on PEA but not on PMA. This work demonstrates an interplay between material chemistry and topology in modulating material-driven FN fibrillogenesis and cell differentiation

Jóvenes investigadores

Ser joven en el siglo XXI, aparte de nuevas miradas para construir mundos, ofrece la oportunidad de encontrar múltiples caminos para realizarse como ser humano. Una de ellas dentro de un contexto de dificultades y desesperanzas provocadas en el marco del conflictivo contexto que vivimos está en la bonita tarea de ser Joven Investigador/a, que consiste en la calidad asumida por quien cumple las condiciones de haber terminado una carrera universitaria, pertenecer a un grupo de investigación y tener hasta 26 años de edad, y estar vinculado con una beca, a costa bien de la universidad o en cofinanciación con Colciencias. Su compromiso es desarrollar durante un año, que puede ser prorrogable, actividades de formación y trabajo como investigador/a. El/la joven responde a unas tareas que incluyen la elaboración de un artículo publicable, el cual se convertirá en la puerta de entrada al mundo de la ciencia. Con el ánimo de poner en evidencia lo que hacen los jóvenes se presenta el primer volumen de esta colección, que representa un texto colectivo resultado del pensar-hacer de algunos de los jóvenes investigadores/as adscritos a los grupos de investigación de la UPTC. La construcción de este volumen implica que se crearon unas condiciones de confianza y reconocimiento institucional a la labor de los jóvenes quienes representan una de las más significativas fortalezas en el proceso de formación investigadora y de ejecución de la investigación. El trabajo de los jóvenes contribuye a aumentar y perfeccionar la capacidad tanto teórica como práctica de los grupos, a la vez que aporta nuevas dinámicas e iniciativas de realización de proyectos, de temas y de modos de vinculación con comunidades y grupos sociales. Para la universidad los jóvenes investigadores/as constituyen un colectivo de creación, transformación y producción de conocimiento. De dicho colectivo, como equipo de trabajo en el interior de los grupos, se espera, ante todo, que profundice su formación de segunda fase, posterior a la de semilleros de investigación, que es el momento inicial para adentrarse en el reconocimiento del sentido, del significado y de los modos de investigación. La formación investigadora del/la joven involucra las potencialidades de resolución de problemas metodológicos y conceptuales de un campo temático que lo habilita para formularse interrogantes, le potencia sus capacidades para enfrentar los ya construidos y avanzar en la interpretación de éstos apoyados en teorías específicas